P1601: PREDICTING THE RESPONSE TO SPLENECTOMY IN IMMUNE THROMBOCYTOPENIA (ITP): A MULTI-CENTRIC PILOT STUDY
Authors: Simone Zoletto, Marco Pizzi, De Crescenzo Andrea, Fabio D’amore, Alberto Friziero, Irene Bertozzi, Giuseppe Carli, Barbara Famengo, Ilaria Nichele, Nicola Vianelli, Giuseppe Auteri, Elena Sabattini, Angelo Paolo Dei Tos, Livio Trentin, Fabrizio Vianello
Journal: HemaSphere (2023)

Topic: 32. Platelet disorders Background: Primary immune thrombocytopenia (ITP) is an acquired disorder characterized by immune-mediated platelet destruction. The spleen is a major player as it orchestrates the immune system derangement and it represents the major site of autoantibody production. This is nicely backed up by evidence-based effectiveness of splenectomy, which offers the highest rates of durable response. In spite of being the most effective curative treatment, splenectomy currently represents a last resort after failure of all the medical armamentarium, understandably due to the unpredictable long-term outcome which does not outbalance the drawbacks of an irreversible surgical approach. In such a context, a better prediction of response may redefine the timing of splenectomy, greatly supporting the management of ITP patients. Preliminary observations from our group highlighted a possible relationship between splenectomy response and a combination of clinical-histological parameters. To address this in more detail, we expanded our original observations to a multi-centric Italian study. Aims: This study aimed to (i) investigate clinical-histological predictors of splenectomy response in ITP patients; (ii) provide an easy-to-use score to predict splenectomy response. Methods: This retrospective, multi-centric study considered a discovery (n=25) and a validation set (n=39) of adult ITP patients, who underwent splenectomy for refractory disease in three Italian referral centers for ITP (Padua and Bologna University Hospitals; San Bortolo Hospital of Vicenza). The inclusion criteria were set as follows: availability of clinical-laboratory data (age at diagnosis; autoimmune comorbidities; bleeding symptoms; pre-splenectomy therapies; platelet counts pre/post-splenectomy); availability of splenic samples for histological analysis; clinical follow-up ≥3 months. Response to splenectomy was assessed by IWG criteria. In the discovery set, variables even marginally associated with surgical outcome (p<0.1) were combined in a clinical score, following assessment of the best cut-off values by ROC analysis. The score was then applied to the validation set. Survival analyses were run with log-rank test and Kaplan-Meier curves. Differences were considered statistically significant for p-values <0.05. Results: In the discovery set, post-splenectomy ITP recurrence was significantly associated with age at diagnosis ≥50 years (p=0.03). A trend toward statistical significance was also noted with presence of autoimmune comorbidities and with steroid administration (≥0.5 mg/kg/day) in the days immediately before surgery (p=0.06). The combination of such variables into an integrated score (1 point for each factor) disclosed higher relapse rates in patients with scores ≥1 (Positive Predictive Value [PPV]: 50%; Negative Predictive Value [NPV]: 100%; 1-year relapse-free survival [RFS]: 53% vs 100% with score ≥1 vs score =0; median follow up: 68 months; p=0.02). These results were confirmed in the validation set (PPV: 55%; NPV: 82%; 1-year RFS: 54% vs 89% with score ≥1 vs score =0; median follow up: 56 months; p=0.01). Of note, some histological parameters (i.e. low T follicular helper cell density and marginal zone atrophy) identified a small subset of patients at high risk of early post-splenectomy recurrence. Summary/Conclusion: An integrated set of clinical parameters (age at diagnosis; autoimmune comorbidities; pre-splenectomy steroid dosage ≥0.5 mg/kg/day) may predict splenectomy response in ITP. Histological evaluation adds to the identification of patients at high-risk of post-splenectomy relapse.Keywords: ITP, Chronic ITP, Immune thrombocytopenia (ITP), Splenectomy